Although heart disease is widely proclaimed to be a major "killer" in the U.S. (600,000 deaths/yr due to coronary ischemia), the fact that many are due to brain death and about 20% of survivors have permanent brain damage is neglected. 800,000 deaths/yr occur rom medical and surgical emergencies and 10,000 from accidents frequently involving head and chest injuries. The importance of the brain in resuscitation arises from the following: 1) It has an extremely high metabolic rate (represents 1-2% of body weight, consumes 15% of the oxygen and receives 15-20% of the total cardiac output) making it most sensitive to oxygen lack; 2) advances in cardio-pulmonary resuscitation are not paralleled by advances in resuscitation of the brain and 3) improved ambulance services (Mobile Intensive Care Units) and approval of the Emergency Medical Services Act by Congress will result in a greater number of cases requiring treatment for post-ischemic-anoxic encephalopathy (PIAE). Locialized brain injury frequently leads to total brain death. The mechanism of this is not clearly understood. Brain circulation and oxygen consumption gradually decrease until both are essentially zero with brain death. Different regions of the brain vary in susceptibility to ischemic-anoxia and following cardiac arrest, regions suffering earliest damage may form foci which gradually expand to ultimately involve the entire brain. Our aim is to determine the pathophysiologic changes in regional brain tissue pH, PO2, pressure and blood flow to determine what if any, pathophysiologic alterations may be implicated in the development of PIAE and what factors differentiate areas of high vulnerability. Of the cerebral cortex, the occipital and parietal cortices appear most vulnerable whereas the frontal and temporal, the least. Using a monkey model we have recently developed (neck tourniquet occlusion with other features) we will evaluate a variety of therapeutic procedures (hemodilution, osmotherapy, thiopental, i.v. xylocaine, steroids, hypertension, hyperventilation and a combination of the above) in altering the course of the post-ischemic pathophysiologic changes. Knowledge of the specific pathophysiologic alterations that occur will help develop new therapeutic procedures.